title: Down-regulation of hypothalamic pro-opiomelanocortin (POMC) expression after weaning is associated with hyperphagia-induced obesity in JCR rats overexpressing neuropeptide Y.
abstract: We hypothesised that hypothalamic feeding-related neuropeptides are differentially expressed in obese-prone and lean-prone rats and trigger overeating-induced obesity. To test this hypothesis, in the present study, we measured energy balance and hypothalamic neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) mRNA expressions in male JCR:LA-cp rats. We compared, in independent cohorts, free-feeding obese-prone (Obese-FF) and lean-prone (Lean-FF) rats at pre-weaning (10 d old), weaning (21-25 d old) and early adulthood (8-12 weeks). A group of Obese-pair-feeding (PF) rats pair-fed to the Lean-FF rats was included in the adult cohort. The body weights of 10-d-old Obese-FF and Lean-FF pups were not significantly different. However, when the pups were shifted from dams' milk to solid food (weaning), the obese-prone rats exhibited more energy intake over the days than the lean-prone rats and higher body and fat pad weights and fasting plasma glucose, leptin, insulin and lipid levels. These differences were consistent with higher energy consumption and lower energy expenditure. In the young adult cohort, the differences between the Obese-FF and Lean-FF rats became more pronounced, yielding significant age effects on most of the parameters of the metabolic syndrome, which were reduced in the Obese-PF rats. The obese-prone rats displayed higher NPY expression than the lean-prone rats at pre-weaning and weaning, and the expression levels did not differ by age. In contrast, POMC expression exhibited significant age-by-genotype differences. At pre-weaning, there was no genotype difference in POMC expression, but in the weanling cohort, obese-prone pups exhibited lower POMC expression than the lean-prone rats. This genotype difference became more pronounced at adulthood. Overall, the development of hyperphagia-induced obesity in obese-prone JCR rats is related to POMC expression down-regulation in the presence of established NPY overexpression.
authors.affiliation: Metabolic and Cardiovascular Diseases Laboratory, Alberta Institute for Human Nutrition, Alberta Diabetes Institute, University of Alberta, Edmonton, Canada.
authors.forename: Abdoulaye
authors.initials: A
authors.lastname: Diané
authors.affiliation: Department of Sociology, University of Alberta, H.M Tory Building, Edmonton, Canada, AB T6G 2H4.
authors.forename: W David
authors.initials: WD
authors.lastname: Pierce
authors.affiliation: Metabolic and Cardiovascular Diseases Laboratory, Alberta Institute for Human Nutrition, Alberta Diabetes Institute, University of Alberta, Edmonton, Canada.
authors.forename: James C
authors.initials: JC
authors.lastname: Russell
authors.affiliation: Department of Psychology, University of Alberta, Edmonton, Canada.
authors.forename: C Donald
authors.initials: CD
authors.lastname: Heth
authors.affiliation: Metabolic and Cardiovascular Diseases Laboratory, Alberta Institute for Human Nutrition, Alberta Diabetes Institute, University of Alberta, Edmonton, Canada.
authors.forename: Donna F
authors.initials: DF
authors.lastname: Vine
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval, Quebec, Canada.
authors.forename: Denis
authors.initials: D
authors.lastname: Richard
authors.affiliation: Metabolic and Cardiovascular Diseases Laboratory, Alberta Institute for Human Nutrition, Alberta Diabetes Institute, University of Alberta, Edmonton, Canada.
authors.forename: Spencer D
authors.initials: SD
authors.lastname: Proctor
mesh_terms: D050154:Adiposity; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D001522:Behavior, Animal; D031204:Caloric Restriction; D015536:Down-Regulation; D002149:Energy Intake; D004734:Energy Metabolism; D018507:Gene Expression Regulation, Developmental; D006963:Hyperphagia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000517:prevention & control; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000209:etiology* / Q000517:prevention & control; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011922:Rats, Mutant Strains; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D014886:Weaning
chemical_list: D009478:Neuropeptide Y; D012333:RNA, Messenger; D054411:Receptors, Leptin; D011333:Pro-Opiomelanocortin